[unreadable] Type 1 diabetes mellitus is a major health problem affecting millions of people worldwide. Despite extensive attempts at clinical management of type 1 diabetes, many patients will develop long-term complications including retinopathy, nephropathy, neuropathy and cardiovascular disease. The Diabetes Control and Complication Trial (DCCT), and it's follow-up study called Epidemiology of Diabetes Interventions Complications (EDIC) is a large multi-center clinical trial of blood glucose control in type 1 diabetes and it's effect on diabetic complications. This study has shown that tight control of blood glucose in type 1 diabetes is associated with a reduction in long term complications including diabetic retinopathy, nephropathy, neuropathy and cardiovascular disease. In addition, this study has shown that there is clustering of the diabetic complications of nephropathy and retinopathy in families, providing evidence that variations in genetic factors (genes) contribute to these complications. Using a combination of laboratory and statistical analyses, we aim to identify the genes that contribute to the differences in risk of diabetic complications by studying DMA samples provided by 1,419 individuals and 2,978 of their relatives from the DCCT/EDIC study as well as 1,759 individuals (and 956 relatives) from another study of diabetic nephropathy, GoKinD, (an 'extreme case' 'extreme-control' study). We will use clinical data collected over the last 20 years from DCCT/EDIC which include repeated measures of diabetes complications and appropriate risk factors as well as data from the GoKinD study. We will test about 550,000 common variations in the genome across the whole of the genome for association with retinal and renal complications of type 1 diabetes. In addition, the same variations will be tested for association with risk factors for cardiovascular disease, intermediate measures of atherosclerosis and clinical neuropathy. Through this initiative, we will provide insights into the basic genetic mechanisms that underlie the long-term complications of type 1 diabetes. The information obtained will assist caregivers of individuals with type 1 diabetes predict the risk of developing specific diabetic complications, and may change treatment strategies, therapeutics, and prognosis for people with type 1 diabetes. [unreadable] [unreadable]